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Previous Depression Research: 2002-2006   
The Depression File also contains summaries of past research that has shown promise and may still be standard practice among many physicians. To download earlier research findings on Depression, click HERE.
 

Latest Research on Depression
     
Am J Psychiatry. 2008 Aug;165(8):969-77. Epub 2008 Jul 15.
The evolution of the cognitive model of depression and its neurobiological correlates.
Beck AT.
Department of Psychiatry, University of Pennsylvania, 3535 Market St., Rm. 2032, Philadelphia, PA 19104, USA. abeck@mail.med.upenn.edu

Although the cognitive model of depression has evolved appreciably since its first formulation over 40 years ago, the potential interaction of genetic, neurochemical, and cognitive factors has only recently been demonstrated. Combining findings from behavioral genetics and cognitive neuroscience with the accumulated research on the cognitive model opens new opportunities for integrated research. Drawing on advances in cognitive, personality, and social psychology as well as clinical observations, expansions of the original cognitive model have incorporated in successive stages automatic thoughts, cognitive distortions, dysfunctional beliefs, and information-processing biases. The developmental model identified early traumatic experiences and the formation of dysfunctional beliefs as predisposing events and congruent stressors in later life as precipitating factors. It is now possible to sketch out possible genetic and neurochemical pathways that interact with or are parallel to cognitive variables. A hypersensitive amygdala is associated with both a genetic polymorphism and a pattern of negative cognitive biases and dysfunctional beliefs, all of which constitute risk factors for depression. Further, the combination of a hyperactive amygdala and hypoactive prefrontal regions is associated with diminished cognitive appraisal and the occurrence of depression. Genetic polymorphisms also are involved in the overreaction to the stress and the hypercortisolemia in the development of depression--probably mediated by cognitive distortions. I suggest that comprehensive study of the psychological as well as biological correlates of depression can provide a new understanding of this debilitating disorder.

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Arch Gen Psychiatry. 2008 Aug;65(8):897-905.
Testing causality in the association between regular exercise and symptoms of anxiety and depression.
De Moor MH, Boomsma DI, Stubbe JH, Willemsen G, de Geus EJ.
Department of Biological Psychology, VU University Amsterdam, van der Boechorststraat 1, 1081 BT Amsterdam, The Netherlands. mhm.de.moor@psy.vu.nl

CONTEXT: In the population at large, regular exercise is associated with reduced anxious and depressive symptoms. Results of experimental studies in clinical populations suggest a causal effect of exercise on anxiety and depression, but it is unclear whether such a causal effect also drives the population association. We cannot exclude the major contribution of a third underlying factor influencing exercise behavior and symptoms of anxiety and depression. OBJECTIVE: To test causal effects of exercise on anxious and depressive symptoms in a population-based sample. DESIGN: Population-based longitudinal study (1991-2002) in a genetically informative sample of twin families. SETTING: Causal effects of exercise were tested by bivariate genetic modeling of the association between exercise and symptoms of anxiety and depression, correlation of intrapair differences in these traits among genetically identical twins, and longitudinal modeling of changes in exercise behavior and anxious and depressive symptoms. PARTICIPANTS: A total of 5952 twins from the Netherlands Twin Register, 1357 additional siblings, and 1249 parents. All participants were aged 18 to 50 years. MAIN OUTCOME MEASUREMENTS: Survey data about leisure-time exercise (metabolic equivalent task hours per week based on type, frequency, and duration of exercise) and 4 scales of anxious and depressive symptoms (depression, anxiety, somatic anxiety, and neuroticism, plus a composite score). RESULTS: Cross-sectional and longitudinal associations were small and were best explained by common genetic factors with opposite effects on exercise behavior and symptoms of anxiety and depression. In genetically identical twin pairs, the twin who exercised more did not display fewer anxious and depressive symptoms than the co-twin who exercised less. Longitudinal analyses showed that increases in exercise participation did not predict decreases in anxious and depressive symptoms. CONCLUSION: Regular exercise is associated with reduced anxious and depressive symptoms in the population at large, but the association is not because of causal effects of exercise.

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J Adolesc Health. 2008 Aug;43(2):180-7. Epub 2008 Apr 11.
Adolescent school failure predicts later depression among girls.
McCarty CA, Mason WA, Kosterman R, Hawkins JD, Lengua LJ, McCauley E.
Department of Pediatrics, University of Washington, Seattle, Washington, USA. cmccarty@u.washington.edu

PURPOSE: Past research has found that social, academic, and behavioral problems are linked with depression during childhood and adolescence. The present study tests a longitudinal cascade model of adolescent problems predicting depression into adulthood, while additionally testing for gender differences. METHODS: Using prospective longitudinal analysis with a sample of 808 youth followed from age 10 to 21, we tested whether social problems, school failure, and delinquency in adolescence increased risk for a major depressive episode in emerging adulthood. Structural equation modeling was used to test for gender differences. RESULTS: Both early conduct problems and adolescent school failures predisposed girls to depression in young adulthood. Among the boys, none of the problems conferred risk for depression. CONCLUSIONS: This study highlights the mutual interplay between school failure and psychological functioning. It is suggested that school adaptation in adolescence be considered a mental health issue.

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Psychiatr Genet. 2008 Aug;18(4):162-6.
Angiotensinogen M235T polymorphism and symptoms of depression in a population-based study and a family-based study.
López-León S, Janssens AC, Tiemeier H, Hofman A, Aulchenko YS, Snijders PJ, Claes S, Oostra BA, van Duijn CM.
Department of Epidemiology and Biostatistics, Erasmus University Medical Center, Rotterdam, The Netherlands.

BACKGROUND: Evidence suggests that the angiotensinogen (AGT) gene is involved in depression. The aim of this paper is to examine the association between the AGT M235T polymorphism and symptoms of depression in two independent populations; a population-based study, and a family-based study. METHODS: Symptoms of depression were scored using the Centre of Epidemiological Studies Depression Scale (CES-D) and compared between the MM, MT, and TT genotype groups. The extent to which AGT M235T explains the heritability of the scores was examined using a variance components analysis. RESULTS: A significant relationship between the AGT M235T polymorphism and CES-D scores was found in men in both populations. The heritability estimate was 32%. The AGT genotype contributed to 1% of the total variance of the CES-D scores. CONCLUSION: Our findings suggest that the AGT gene is involved in the aetiology of symptoms of depression in men.

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Neuron. 2008 Jul 31;59(2):185-6. Comment on: Neuron. 2008 Jul 31;59(2):207-13.
Understanding the pathophysiology of postpartum depression: implications for the development of novel treatments.
Nemeroff CB.
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA 30322, USA. cnemero@emory.edu

Depression during pregnancy and in the postpartum period is common, devastating to mothers and their offspring, and poorly understood in terms of pathophysiology. In this issue of Neuron, Maguire and Mody provide evidence for a role for aberrant neurosteroid regulation of the GABA(A) receptor subunit in the etiology of postpartum depression, presaging elucidation of the pathophysiology and development of treatments of this depression endophenotype.

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Lancet. 2008 Jul 5;372(9632):40-8. Comment in: Lancet. 2008 Jul 5;372(9632):8-10.
Management of depression for people with cancer (SMaRT oncology 1): a randomised trial.
Strong V, Waters R, Hibberd C, Murray G, Wall L, Walker J, McHugh G, Walker A, Sharpe M.
University of Edinburgh Cancer Research Centre, Western General Hospital, Crewe Road, Edinburgh, UK.

BACKGROUND: Major depressive disorder severely impairs the quality of life of patients with medical disorders such as cancer, but evidence to guide its management is scarce. We aimed to assess the efficacy and cost of a nurse-delivered complex intervention that was designed to treat major depressive disorder in patients who have cancer. METHODS: We did a randomised trial in a regional cancer centre in Scotland, UK. 200 outpatients who had cancer with a prognosis of greater than 6 months and major depressive disorder (identified by screening) were eligible and agreed to take part. Their mean age was 56.6 (SD 11.9) years, and 141 (71%) were women. We randomly assigned 99 of these participants to usual care, and 101 to usual care plus the intervention, with minimisation for sex, age, diagnosis, and extent of disease. The intervention was delivered by a cancer nurse at the centre over an average of seven sessions. The primary outcome was the difference in mean score on the self-reported Symptom Checklist-20 depression scale (range 0 to 4) at 3 months after randomisation. Analysis was by intention to treat. This trial is registered as ISRCTN84767225. FINDINGS: Primary outcome data were missing for four patients. For 196 patients for whom we had data at 3 months, the adjusted difference in mean Symptom Checklist-20 depression score, between those who received the intervention and those who did not, was 0.34 (95% CI 0.13-0.55). This treatment effect was sustained at 6 and 12 months. The intervention also improved anxiety and fatigue but not pain or physical functioning. It cost an additional pound sterling 5278 (US$10 556) per quality-adjusted life-year gained. INTERPRETATION: The intervention-Depression Care for People with Cancer-offers a model for the management of major depressive disorder in patients with cancer and other medical disorders who are attending specialist medical services that is feasible, acceptable, and potentially cost effective.

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Am J Geriatr Psychiatry. 2008 Jul;16(7):558-67.
Efficacy of second generation antidepressants in late-life depression: a meta-analysis of the evidence.
Nelson JC, Delucchi K, Schneider LS.
Department of Psychiatry, University of California San Francisco, CA, USA. craign@lppi.ucsf.edu

OBJECTIVE: Second-generation antidepressants are commonly used to treat major depression in late-life. This systematic review and meta-analysis was undertaken to assess the evidence for efficacy of second-generation antidepressants in late-life major depression. METHODS: The Cochrane Library (2006 [3]), MEDLINE (1966 to August 2006), and meeting presentations were searched for trials of second-generation antidepressants (nontricyclics) marketed in the United States. Published and unpublished placebo-controlled randomized clinical trials in outpatients 60 years and older, with nonpsychotic, unipolar major depression were selected. Clinical characteristics and outcomes were extracted. Outcomes were expressed as odds ratios (OR), risk differences, and weighted mean differences. RESULTS: Ten unique trials (four unpublished) with 13 contrasts met selection criteria. Trials were 6-12 weeks duration, and included 2,377 patients who received active drug and 1,788 received placebo. The ORs by meta-analysis for response and remission were 1.40 (95% confidence interval [CI] 1.24-1.57, z = 5.45, N = 13, p <0.001) and 1.27 (CI 1.12-1.44, z = 3.67, N = 13, p <0.001), respectively, with significant heterogeneity for response and remission among the trials. Mean pooled response rates for antidepressant and placebo were 44.4% and 34.7%, respectively. The OR for response was significantly higher in the 10-12 week trials (OR = 1.73, CI 1.42-2.09, z = 5.51, N = 5, p <0.001) than the 6-8 week trials (OR = 1.22, CI 1.05-1.42, z = 2.60, N = 8, p = 0.01). ORs for discontinuation for any reason and for adverse events were significantly higher with drugs than with placebo. CONCLUSIONS: Antidepressants are more effective than placebo in elderly depressed subjects although effects are modest and vary. Identification of the characteristics of responders and nonresponders will be crucial to improving treatment outcomes.

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Ann Fam Med. 2008 Jul-Aug;6(4):295-301.
Integration of depression and hypertension treatment: a pilot, randomized controlled trial.
Bogner HR, de Vries HF.
Department of Family Medicine and Community Health, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. hillary.bogner@uphs.upenn.edu

PURPOSE: We wanted to examine whether integrating depression treatment into care for hypertension improved adherence to antidepressant and antihypertensive medications, depression outcomes, and blood pressure control among older primary care patients. METHODS: Older adults prescribed pharmacotherapy for depression and hypertension from physicians at a large primary care practice in West Philadelphia were randomly assigned to an integrated care intervention or usual care. Outcomes were assessed at baseline, 2, 4, and 6 weeks using the Center for Epidemiologic Studies Depression Scale (CES-D) to assess depression, an electronic monitor to measure blood pressure, and the Medication Event Monitoring System to assess adherence. RESULTS: In all, 64 participants aged 50 to 80 years participated. Participants in the integrated care intervention had fewer depressive symptoms (CES-D mean scores, intervention 9.9 vs usual care 19.3; P <.01), lower systolic blood pressure (intervention 127.3 mm Hg vs usual care 141.3 mm Hg; P <.01), and lower diastolic blood pressure (intervention 75.8 mm Hg vs usual care 85.0 mm Hg; P <.01) compared with participants in the usual care group at 6 weeks. Compared with the usual care group, the proportion of participants in the intervention group who had 80% or greater adherence to an antidepressant medication (intervention 71.9% vs usual care 31.3%; P <.01) and to an antihypertensive medication (intervention 78.1% vs usual care 31.3%; P <.001) was greater at 6 weeks. CONCLUSION: A pilot, randomized controlled trial integrating depression and hypertension treatment was successful in improving patient outcomes. Integrated interventions may be more feasible and effective in real-world practices, where there are competing demands for limited resources.

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CA Cancer J Clin. 2008 Jul-Aug;58(4):214-30. Epub 2008 Jun 16.
Psychosocial interventions for anxiety and depression in adult cancer patients: achievements and challenges.
Jacobsen PB, Jim HS.
Department of Psychology, University of South Florida, Tampa, FL, USA.

Psychosocial care is increasingly recognized as an essential component of the comprehensive care of the individual with cancer. Improving patients' access to psychosocial care is important; however, ensuring that the care made available has been shown to be effective is just as important. Accordingly, the goal of this review is to describe an evidence-based approach to the psychosocial care of adults with cancer. The focus is on anxiety and depression because a considerable body of research has examined the impact of psychosocial interventions on these outcomes. After describing the sources, assessment, and prevalence of anxiety and depression in adults with cancer and presenting existing clinical practice guidelines for their management, previous publications that systematically reviewed evidence of the efficacy of psychosocial interventions are summarized. The use of these publications to derive specific recommendations for the use of psychosocial interventions in the management of anxiety and depression is then illustrated. In addition, examples are provided of interventions that are effective against anxiety and depression and have good potential for dissemination in routine clinical practice. The review concludes with a discussion of future directions for the continued development of an evidence-based approach to the psychosocial care of people with cancer.

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CNS Spectr. 2008 Jul;13(7):561-5.
Depression, anhedonia, and psychomotor symptoms: the role of dopaminergic neurocircuitry.
Stein DJ.
Department of Psychiatry and Mental Health, University of Cape Town, South Africa.

The heterogeneity of major depression suggests that multiple neurocircuits and neurochemicals are involved in its pathogenesis. Anhedonia and psychomotor symptoms are, however, particularly characteristic features of major depression and may provide insights into its underlying psychobiology. Importantly, these symptoms appear to be mediated by dopaminergic mesolimbic and mesostriatal projections, the function of which is, in turn, influenced by key gene variants and environment stressors. Indeed, there is growing evidence of the way in which the dopaminergic system is associated with cognitive-affective disturbances in depression, and provides a useful target for therapeutic interventions. At the same time, a range of other systems are likely to contribute to the psychobiology of this condition.

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Gen Hosp Psychiatry. 2008 Jul-Aug;30(4):293-302.
Psychological interventions for major depression in primary care: a meta-analytic review of randomized controlled trials.
Bortolotti B, Menchetti M, Bellini F, Montaguti MB, Berardi D.
Institute of Psychiatry, Bologna University, Viale C. Pepoli, 5IT-40123 Bologna, Italy. biancamaria.bortolotti@unibo.it

OBJECTIVE: Various studies have tested psychological therapies in the treatment of depression in primary care. Yet, concerns over their clinical effectiveness, as compared to usual general practitioner (GP) care or treatment with antidepressants, have been raised. The present meta-analysis was aimed at assessing currently available evidence on the topic. METHOD: A systematic search of electronic databases identified 10 randomized controlled trials comparing psychological forms of intervention with either usual GP care or antidepressant medication for major depression. Meta-analytical procedures were used to examine the impact of psychological intervention in primary care on depression, as compared to usual GP care and antidepressant treatment. RESULTS: The main analyses showed greater effectiveness of psychological intervention over usual GP care in both the short term [standardized mean difference (SMD)=-0.42, 95% confidence interval (CI)=-0.59 to -0.26, n=408] and long term (SMD=-0.30, 95% CI=-0.45 to -0.14, n=433). The heterogeneity test was not significant in the short term at the P<.05 level (df=5, P=.57, I(2)=0%), but it was significant in the long term (df=5, P=.004, I(2)=70.9%). The comparison between psychological forms of intervention and antidepressant medication yielded no effectiveness differences, for either the short term or the long term. CONCLUSIONS: Psychological forms of intervention are significantly linked to clinical improvement in depressive symptomatology and may be useful for supplementing usual GP care.

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Ned Tijdschr Geneeskd. 2008 Jun 21;152(25):1413-7.
[Immune activation and depression in the elderly]
[Article in Dutch]
Maas DW, Westendorp RG, van der Mast RC.
Leids Universitair Medisch Centrum, afd. Psychiatrie, B1-P, Postbus 9600, 2300 RC Leiden. d.w.maas@lumc.nl

Besides the monoamine hypothesis, the stress hypothesis and the vascular hypothesis, the inflammatory hypothesis might be an etiological explanation for late-life depression. There is a growing amount of evidence to support this hypothesis. In animal studies, injection with cytokines was shown to cause behavioural changes ('sickness behaviour') similar to depressive symptoms in humans. Cytokine treatment of certain tumours and chronic hepatitis can also cause depressive symptoms. The prevalence of depression in patients with autoimmune diseases is higher than in the general population. Etanercept had a favourable effect on the depressive symptoms in patients with psoriasis, independent of improvement of physical symptoms. Cytokines affect the hypothalamus-pituitary-adrenal axis and cerebral neurotransmitter systems, both of which are thought to be involved in depression. Immune activation has been associated with depression, and several anti-depressive treatments affect immune parameters, although inconsistently. Since the aging process is associated with a dysregulation of the immune system, the inflammation hypothesis might be particularly true in late-life depression.

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Med J Aust. 2008 Jun 16;188(12 Suppl):S138-41.
Preventing relapse of depression in primary care: a pilot study of the "Keeping the blues away" program.
Howell CA, Turnbull DA, Beilby JJ, Marshall CA, Briggs N, Newbury WL.
Discipline of General Practice, University of Adelaide, Adelaide, SA, Australia. cate.howell@adelaide.edu.au

OBJECTIVES: To determine the effectiveness of "Keeping the blues away" (KBA), a manualised depression relapse prevention program for general practice, in reducing the relapse of depression compared with usual care (with the aim of halving the relapse rate), and in reducing depression severity and improving the process of care. DESIGN AND SETTING: A cluster randomised controlled trial conducted in 2004-2005 in South Australian general practices. PARTICIPANTS: 43 general practitioners from 23 urban and rural practices recruited 110 patients with depression (age range, 18-75 years). INTERVENTION: GP training manual or patient manual and relaxation CD; 20 hours of training on depression, the study protocol, assessment tools and skills. MAIN OUTCOME MEASURES: Relative risk (RR) of depression relapse; depression severity and quality of life scores. RESULTS: There were no significant differences in relapse rates between the groups (chi(2)(1) = 1.51; P = 0.23), although there was a non-significant tendency for relapse to be reduced in the KBA group (RR = 0.77; 95% CI, 0.50-2.05). Older patients (> or = 50 years) in the KBA group showed a significantly lower probability of relapse than those in the control group (P = 0.018). There was a decrease in depression scores in both groups. KBA participants had more severe depression at baseline, and the reduction in severity in those with symptoms for > 6 months was nearly significant (P = 0.06). KBA was positively received by GPs and patients. CONCLUSIONS: Although this pilot study of a small sample did not achieve its primary outcome of reducing depression relapse by 50%, KBA was found to be a promising program for older patients and for those with more severe or persistent symptoms.

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Australas Psychiatry. 2008 Jun;16(3):183-90.
Brain stimulation techniques for the treatment of depression and other psychiatric disorders.
Fitzgerald P.
Alfred Psychiatry Research Centre, The Alfred and Monash University School of Psychology, Psychiatry and Psychological Medicine, VIC, Australia.

OBJECTIVE: The aim of this paper was to review the development of repetitive transcranial magnetic stimulation (rTMS), magnetic seizure therapy (MST), vagal nerve stimulation (VNS), deep brain stimulation (DBS) and other recent brain stimulation techniques for their potential use in the treatment of a range of psychiatric disorders. CONCLUSIONS: A considerable number of studies have been conducted to investigate the efficacy of rTMS. Although there are considerable problems with this research base, globally the studies suggest that rTMS has antidepressant efficacy. However, more research is required to define the most effective way of applying this technique. There is a much smaller research base supporting the use of VNS and to date the research suggests that only a minority of patients benefit from this procedure. Considerably more research is required in the use of the other techniques which at this stage have been tested only to a very small degree. It is likely that one, and possibly a number, of the new brain stimulation techniques will become available clinically in the psychiatric armamentarium in the coming years. However, considerable research is still required to establish efficacy and define the appropriate place in clinical practice for these treatment approaches.

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CNS Spectr. 2008 Jun;13(6):501-10.
Inflammation, glutamate, and glia in depression: a literature review.
McNally L, Bhagwagar Z, Hannestad J.
Yale University School of Medicine, New Haven, CT 06519, USA.

Multiple lines of evidence suggest that inflammation and glutamate dysfunction contribute to the pathophysiology of depression. In this review we provide an overview of how these two systems may interact. Excess levels of inflammatory mediators occur in a subgroup of depressed patients. Studies of acute experimental activation of the immune system with endotoxin and of chronic activation during interferon-alpha treatment show that inflammation can cause depression. Peripheral inflammation leads to microglial activation which could interfere with excitatory amino acid metabolism leading to inappropriate glutamate receptor activation. Loss of astroglia, a feature of depression, upsets the balance of anti- and pro-inflammatory mediators and further impairs the removal of excitatory amino acids. Microglia activated by excess inflammation, astroglial loss, and inappropriate glutamate receptor activation ultimately disrupt the delicate balance of neuroprotective versus neurotoxic effects in the brain, potentially leading to depression.

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Int Clin Psychopharmacol. 2008 May;23(3):113-9.
Venlafaxine extended release versus citalopram in patients with depression unresponsive to a selective serotonin reuptake inhibitor.
Lenox-Smith AJ, Jiang Q.
aWyeth UK, Huntercombe Lane South, Slough, UK bWyeth Research, Collegeville, Pennsylvania, USA.

Findings from the National Institute of Mental Health's Sequenced Treatment Alternatives to Relieve Depression trial indicate that approximately 50% of patients with major depressive disorder do not experience a treatment response after adequate first-line treatment with a selective serotonin reuptake inhibitor (SSRI). This study was designed to test the hypothesis that, after treatment failure with an SSRI, switching to venlafaxine extended release (ER) would offer advantages over switching to another SSRI, citalopram. The objectives of this trial were to compare the efficacy and safety of venlafaxine ER and citalopram in the treatment of moderate-to-severe depression in patients who did not experience a treatment response to an SSRI other than citalopram and to investigate the effects of severity of depression by categorizing treatment groups according to baseline severity. This was a 12-week, double-blind, randomized, parallel-group, multicenter study. Participants were adult outpatients who, following 8 weeks of monotherapy with an adequate dosing regimen of an SSRI other than citalopram and had not responded, met the diagnostic criteria for depression as described in the Diagnostic and statistical manual of mental disorders, fourth edition, and had a score >/=20 on the 21-item Hamilton Rating Scale for Depression (HAM-D21). After a 7-day screening period, patients were randomly assigned to receive venlafaxine ER 75 mg/day or citalopram 20 mg/day for the first 2 weeks. Doses could be increased every 2 weeks through week 6. Treatment lasted 12 weeks and was followed by a 1-week tapering period. Maximum dosages were venlafaxine ER 300 mg/day or citalopram 60 mg/day. The primary end point was the final on-therapy total HAM-D21 score. To investigate the treatment effects of the severity of depression on efficacy, a subgroup analysis was performed for baseline HAM-D21 total score </=31 and >31. The analyses for HAM-D21, Montgomery-Asberg Depression Rating Scale (MADRS), Clinical Global Impressions - Severity (CGI-S), and Clinical Global Impressions - Improvement scores were based on intent-to-treat (ITT) population, for both the primary analysis and subgroup analysis according to baseline HAM-D21 total scores </=31 or >31. Safety assessments included the recording of adverse events (AEs). A total of 406 patients (200 venlafaxine ER, 206 citalopram) were randomly assigned and 396 patients were included in the ITT population (194 venlafaxine ER, 202 citalopram). Treatment groups were similar in terms of demographics and baseline psychiatric assessments. Two hundred and eighty-four patients (137 venlafaxine ER, 147 citalopram) were present in the ITT population with a baseline HAM-D21 total score </=31 and 112 patients (57 venlafaxine ER, 55 citalopram) in the >31 group. In the primary analysis, there was no statistical difference between groups. The group with a baseline HAM-D21 total score of 20-31 did not differ significantly in any efficacy parameters. In the group with a baseline HAM-D21 total score >31, the venlafaxine ER group differed significantly from the citalopram group on the primary end point HAM-D21 total score (P=0.0121). The secondary end point CGI-S score was statistically significant (P=0.0359), although the MADRS total score (P=0.0930) was not. AEs were reported by 57.8 and 63.4% of venlafaxine ER and citalopram patients, respectively. Overall discontinuation rates were 24.5% for venlafaxine ER and 20.9% for citalopram. Discontinuation rates owing to an AE as a primary or secondary reason were 5.5% for venlafaxine ER and 5.3% for citalopram. Overall, venlafaxine ER and citalopram showed similar efficacy in patients who had an inadequate response to an SSRI. In the subset of more severely depressed patients, venlafaxine ER was significantly more effective on a number of efficacy measures. Patients who remain severely depressed following treatment with an SSRI may gain more benefit from the dual-action drug venlafaxine, rather than switching to another SSRI.

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Med Sci Sports Exerc. 2008 Apr 9 [Epub ahead of print]
Depressive Symptoms and Physical Activity in Adolescent Girls.
Johnson CC, Murray DM, Elder JP, Jobe JB, Dunn AL, Kubik M, Voorhees C, Schachter K.
1Tulane University School of Public Health & Tropical Medicine, New Orleans, LA; 2The Ohio State University, Columbus, OH; 3San Diego State University, San Diego, CA; 4National Heart, Lung, and Blood Institute, Bethesda, MD; 5Klein Buendel, Inc., Golden, CO; 6University of Minnesota, Minneapolis, MN; 7University of Maryland, College Park, MD; and 8University of Arizona, Tucson, AZ.

PURPOSE:: To evaluate the relationship between depressive symptoms and physical activity in a geographically and ethnically diverse sample of sixth-grade adolescent girls. METHODS:: The Trial of Activity for Adolescent Girls (TAAG) baseline measurement included a random sample (N = 1721) of sixth-grade girls in 36 schools at six field sites. Measurements were accelerometry and the 3-d Physical Activity Recall (3DPAR) for physical activity, and the Center for Epidemiological Studies-Depression scale (CES-D) for depressive symptoms. RESULTS:: Girls with complete data (N = 1397), mean age 12 yr, had an average CES-D score of 14.7 (SD = 9.25) and engaged in an average of about 460 min of sedentary activity, < 24 min of moderate to vigorous physical activity (MVPA), and < 6 min of vigorous physical activity (VPA) in an 18-h day. Thirty-minute segments of MVPA ranged in number from 3.9 to 1.2, and METS for these segments ranged from > 3.0 to > 6.5. Mixed-model regression indicated no relationship between depressive symptoms and physical activity; however, a significant but modest inverse relationship between sedentary activity and depressive symptoms was observed. CONCLUSION:: A sufficient sample size, standardized procedures, and validated instruments characterized this study; however, a relationship between depressive symptoms and physical activity was not observed for sixth-grade girls from diverse geographic locations. The average CES-D score was lower than is considered clinically meaningful for either adolescents or adults, and MET-minutes of sedentary activity were high. This combination of data may be different from other studies and could have contributed to the unexpected finding. This unexpected finding is informative, however, because it shows the need for additional research that includes a wider range of possible combinations of data, especially with young adolescent girls.

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J Occup Environ Med. 2008 Apr;50(4):459-67.
Population-based care of depression: team care approaches to improving outcomes.
Katon WJ, Seelig M.
From the Department of Psychiatry & Behavioral Sciences (Dr Katon), University of Washington School of Medicine, Seattle, Wash; and Puget Sound Health Alliance (Dr Seelig), Seattle, Wash.

OBJECTIVE:: To describe evidence-based quality improvement interventions in the primary care system that have been shown in randomized trials to the improve quality of care and outcomes of patients with depression. METHODS:: Medical literature review, focused on the concept of population-based care and research-proven ways to decrease the prevalence of depression in primary care, including several meta-analyses that described the effect of collaborative care interventions in improving the quality and outcomes of primary care patients with depression. RESULTS:: A total of 37 randomized trials of collaborative care interventions have shown that collaborative care, compared with usual primary care, is associated with 2-fold increases in antidepressant adherence, improvements in depressive outcomes that last up to 2 to 5 years, increased patient satisfaction with depression care, and improved primary care satisfaction with treating depression. From a health plan perspective, cost-effectiveness analyses suggest that for most depressed primary care patients, collaborative care is associated with a modest increase in medical costs, but markedly improved depression and functional outcomes. The few studies that have used a societal perspective that included examination of both direct and indirect costs found that collaborative care was associated with overall cost savings. For patients with depression and diabetes and depression and panic disorder, there is evidence that the increase in mental health care costs associated with collaborative care is offset by greater savings in medical costs. CONCLUSION:: Collaborative care is a high value intervention associated with improved quality of care, depression outcomes, and improved patient and primary care physician satisfaction.

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Eur J Neurol. 2008 Apr;15 Suppl 1:21-5.
Depressive symptoms in Parkinson's disease.
Lemke MR.
Department of Psychiatry, University of Kiel, Kiel, Germany. m.lemke@alsterdorf.de

Depression occurs in approximately 45% of all patients with Parkinson's disease (PD), does not correlate with the stage of motor deficits, reduces quality of life independently of motor symptoms and appears to be underrated and undertreated. Anxiety and depression are the risk factors for the development of PD and may be present many years before the appearance of motor symptoms. Studies using functional imaging techniques indicate a primary relationship between depression and PD. Because of overlapping clinical symptoms, the diagnosis is mainly based on subjectively experienced anhedonia and feelings of emptiness. Serotonergic, noradrenergic and dopaminergic mechanisms play key roles in the aetiology of depression in PD. Tricyclic and newer selective antidepressants including serotonin and noradrenaline reuptake inhibitors appear to be effective in treating depression in PD. Selective reuptake inhibitors seem to be better tolerated because of their favourable side-effect profile. Experimental and clinical investigations indicate antidepressive effects for pramipexole. Placebo-controlled studies showed antidepressant effects of pramipexole in patients with different forms of depression. Various studies show that pramipexole improves depression in addition to motor symptoms in patients with PD. Because of the data available as well as clinical reasoning, pramipexole may be used as a first-line treatment in patients with PD and depression.

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J Occup Environ Med. 2008 Apr;50(4):428-36.
A brief review of antidepressant efficacy, effectiveness, indications, and usage for major depressive disorder.
Nierenberg AA, Ostacher MJ, Huffman JC, Ametrano RM, Fava M, Perlis RH.
From the Department of Psychiatry, Massachusetts General Hospital, Boston, Mass.

OBJECTIVE:: Antidepressants treat major depressive disorder (MDD) with the burden of associated side effects and difficulties with compliance. The purpose of this article is to review the efficacy and effectiveness of antidepressants for MDD. METHODS:: The authors conducted a focused review of selected key issues and references relevant to the clinically relevant pharmacologic treatment of MDD. Principles of treatment are reviewed. Antidepressants reviewed include SSRIs, mixed norepinephrine or serotonin uptake inhibitors, dopamine or norepinephrine uptake inhibitors, norepinephrine uptake inhibitors, antidepressants with mixed properties, and monoamine oxidase inhibitors. Augmentation and psychotherapy strategies are reviewed. RESULTS:: Antidepressant efficacy has been established in randomized clinical trials and effectiveness studies for acute and long-term treatment, but many patients do not achieve remission. Augmentation strategies and focused psychotherapy can be helpful. CONCLUSIONS:: Antidepressants help most patients with MDD but some are resistant to treatment and have a difficult long-term course.

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CNS Drugs. 2008;22(5):367-388.
Aripiprazole in the Treatment of Depressive and Anxiety Disorders : A Review of Current Evidence.
Pae CU, Serretti A, Patkar AA, Masand PS.
Department of Psychiatry, Kangnam St Mary’s Hospital, The Catholic University of Korea College of Medicine, Seoul, South KoreaDepartment of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina, USA.

Despite the availability of different classes of drugs for the treatment of depressive and anxiety disorders, there are a number of clinically significant unmet needs, such as a high prevalence of treatment resistance, partial response, subsyndromal symptomatology, recurrence and relapse. With the approval of atypical antipsychotics, which are associated with a lower adverse effect burden than typical antipsychotics, consideration of their off-label use for the treatment of affective disorders and various other psychiatric disorders has become a viable option. However, consideration should be given to the US FDA black box warning indicating that atypical antipsychotics may increase mortality risk, particularly in the elderly population with dementia-related psychosis. There has been much conjecture about the utility of these atypical drugs to facilitate traditional antidepressant therapy, either in combination (from the initiation of therapy) or as adjunctive therapy (in the case of partial/incomplete response). Nevertheless, at present, available evidence from randomized, placebo-controlled trials is sparse, and a formal risk/benefit assessment of the use of these agents in a nonpsychotic patient population is not yet possible.As a representative agent from the atypical antipsychotic class with a novel mechanism of action and a relatively low adverse effect burden, aripiprazole represents an interesting potential treatment for depressive and anxiety disorders. In this review, we focus on the rationale for the use of aripiprazole in these disorders.Preclinical data suggests that aripiprazole has a number of possible mechanisms of action that may be important in the treatment of depressive and anxiety disorders. Such mechanisms include aripiprazole action at serotonin (5-HT) receptors as a 5-HT(1A) partial receptor agonist, a 5-HT(2C) partial receptor agonist and a 5-HT(2A) receptor antagonist. Aripiprazole also acts as a dopamine D(2) partial rec
eptor agonist, and has a possible action at adrenergic receptors. Furthermore, aripiprazole may have possible neuroprotective effects.Clinical studies demonstrate that aripiprazole may be useful in the treatment of bipolar depression, major depressive disorder, treatment-resistant depression and possibly anxiety disorders. Clinical data also suggest that aripiprazole may have a lower adverse effect burden than the other atypical drugs.Future research may confirm the potential utility of aripiprazole in the treatment of depressive and anxiety disorders.

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Br J Gen Pract. 2008 Mar;58(548):178-83.
Feasibility of an exercise intervention for women with postnatal depression: a pilot randomised controlled trial.
Daley A, Winter H, Grimmett C, McGuinness M, McManus R, MacArthur C.
Department of Primary Care and General Practice, University of Birmingham, Birmingham, B15 2TT. a.daley@bham.ac.uk

BACKGROUND: Postnatal depression is a serious mental health problem that may be reduced by exercise. AIM: This study examined the feasibility of an exercise intervention for women with postnatal depression, and assessed which methods of recruitment are most effective. DESIGN OF STUDY: Randomised controlled trial. SETTING: General practice and the community. METHOD: Participants were recruited from various sources and randomised to an exercise intervention or usual care with follow-up at 12 weeks. As well as assessing feasibility, other trial outcomes included exercise participation and self-efficacy for exercise. Levels of depression were assessed but the study was not powered to show a difference in this. RESULTS: The recruitment rate of eligible patients was 23.1%. The highest recruitment rate was via referral from the psychiatric mother and baby unit (9/28; 32.1%), followed by invitation letters from GPs (24/93; 25.8%). Thirty-eight eligible participants were randomised. At follow-up there was no significant difference in exercise participation between groups. The intervention group reported significantly higher self-efficacy for exercise compared to usual care, but depression scores did not differ. CONCLUSION: Exercise participation over the 12-week period was not significantly increased, possibly because it is difficult to motivate women with postnatal depression to exercise, or the intervention was not sufficiently intensive. Eligible patients were recruited into this study but response rates were low. Optimum methods of recruitment in this difficult-to-reach population are required prior to a substantive trial. Further research is imperative given poorly-evidenced recommendations by the National Institute for Health and Clinical Excellence to consider this treatment.

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Tijdschr Psychiatr. 2008;50(4):213-22.
[Augmentation with atypical antipsychotics in the treatment of patients with a therapyresistant depression: a review.]
[Article in Dutch]
Selis MA, Peeters FP.

BACKGROUND: A considerable number of depressed patients are showing resistance to current drug treatment strategies. In such cases it is becoming increasingly common in clinical practice to augment an antidepressant with an atypical antipsychotic (aap). purpose To provide an overview of the scientific evidence for this new strategy, to explain the possible mechanisms of action and to assess the place that augmentation with an aap occupies in the treatment of therapy-resistant non-psychotic depression. METHOD: Various search terms were used to locate relevant articles in Pubmed; these articles were examined for relevant references. results Only 6 randomised controlled trials were found, therefore 7 case reports and 10 open-label studies were included. There seems to be some evidence that augmentation with an aap, particularly olanzapine, is effective. One of the main advantages of this strategy is the fast response, namely within a few weeks or even within a week. In view of the lack of scientific support for augmentation with aaps, this strategy is advisable when other augmentation strategies have proved unworkable or are contraindicated. It must be exercised with caution because the combination therapy can have negative effects on the patient's glucose and lipid metabolism. CONCLUSION: Augmentation with aaps in treatment resistant depression may be a potential useful treatment strategy but its scientific evidence is insufficient to warrant inclusion within current guidelines.

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Tijdschr Psychiatr. 2008;50(1):23-31.
[The efficacy of electroconvulsive therapy in adolescents. A restrospective study.]
[Article in Dutch]
Hegeman JM, Doesborgh SJ, van Niel MC, van Megen HJ.
BACKGROUND: Electroconvulsive therapy (ect) is an effective treatment for depressive disorders in adults and the elderly. For adolescents however, ect is still a controversial treatment because little research has been done into the efficacy and side effects of ect in adolescents and because psychiatrists working with children and adolescents are relatively unfamiliar with this form of treatment. AIM: To investigate the efficacy of ect in adolescents who were treated in Meerkanten between 2000 and 2006 for a therapy-resistant depressive episode and/or suicidal behaviour. METHOD: Scores on the Hamilton Depression Rating Scale or the Montgomery-Asberg Depression Rating Scale before and after ect were compared. The percentage improvement on the depression scales and the percentage of patients who showed an improvement of at least 60% on the scales in the group of adolescents were compared with the percentage improvement in a group of adults treated in Meerkanten. results One-third of the adolescent patients showed an improvement of 60% or more on these scales; the average improvement was 46%. ect was found to be equally effective in adolescents and adults. CONCLUSION: ect is a successful form of treatment for one-third of adolescents with a severe therapy-resistant depressive episode; this is a clinically relevant result for these patients for whom no alternative treatments are available.

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Am J Psychiatry. 2008 Jan 2 [Epub ahead of print]
Difference in Treatment Outcome in Outpatients With Anxious Versus Nonanxious Depression: A STAR*D Report.
Fava M, Rush AJ, Alpert JE, Balasubramani GK, Wisniewski SR, Carmin CN, Biggs MM, Zisook S, Leuchter A, Howland R, Warden D, Trivedi MH.

Objective About half of outpatients with major depressive disorder also have clinically meaningful levels of anxiety. The authors conducted a secondary data analysis to compare antidepressant treatment outcomes for patients with anxious and nonanxious major depression in Levels 1 and 2 of the STAR*D study. Method A total of 2,876 adult outpatients with major depressive disorder, enrolled from 18 primary and 23 psychiatric care sites, received citalopram in Level 1 of STAR*D. In Level 2, a total of 1,292 patients who did not remit with or tolerate citalopram were randomly assigned either to switch to sustained-release bupropion (N=239), sertraline (N=238), or extended-release venlafaxine (N=250) or to continue taking citalopram and receive augmentation with sustained-release bupropion (N=279) or buspirone (N=286). Treatment could last up to 14 weeks in each level. Patients were designated as having anxious depression if their anxiety/somatization factor score from the 17-item Hamilton Depression Rating Scale (HAM-D) was 7 or higher at baseline. Rates of remission and response as well as times to remission and response were compared between patients with anxious depression and those with nonanxious depression. Results In Level 1 of STAR*D, 53.2% of patients had anxious depression. Remission was significantly less likely and took longer to occur in these patients than in those with nonanxious depression. Ratings of side effect frequency, intensity, and burden, as well as the number of serious adverse events, were significantly greater in the anxious depression group. Similarly, in Level 2, patients with anxious depression fared significantly worse in both the switching and augmentation options. Conclusions Anxious depression is associated with poorer acute outcomes than nonanxious depression following antidepressant treatment.

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Am J Geriatr Psychiatry. 2008 Jan;16(1):14-20.
Escitalopram in the acute treatment of depressed patients aged 60 years or older.
Bose A, Li D, Gandhi C.
From Forest Research Institute, Jersey City, NJ.

Objective: The present study examined the efficacy and tolerability of acute escitalopram treatment in depressed patients aged 60 years or older. Methods: Patients aged >/=60 years with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition major depressive disorder were randomized to 12 weeks of double-blind, flexible-dose treatment with escitalopram (10-20 mg/day; N = 130) or placebo (N = 134). The prospectively defined primary efficacy end point was change from baseline to week 12 in Montgomery-Asberg Depression Rating Scale (MADRS) total score using the last observation carried forward approach. Results: A total of 109 (81%) patients in the placebo group and 96 (74%) patients in the escitalopram group completed treatment. Mean age in both groups was approximately 68 years. Mean baseline MADRS scores were 28.4 and 29.4 for the placebo and escitalopram treatment groups, respectively. Escitalopram did not achieve statistical significance compared with placebo
in change from baseline on the MADRS (least square mean difference: -1.34; last observation carried forward). Discontinuation rates resulting from adverse events were 6% for placebo and 11% for escitalopram. Treatment-emergent adverse events reported by >10% of patients in the escitalopram group were headache, nausea, diarrhea, and dry mouth. Conclusions: Escitalopram treatment was not significantly different from placebo treatment on the primary efficacy measure, change from baseline to week 12 in MADRS. In patients aged 60 years or older with major depression, acute escitalopram treatment appeared to be well tolerated.

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J Am Geriatr Soc. 2008 Jan 4 [Epub ahead of print]
Can Counseling and Support Reduce Burden and Depressive Symptoms in Caregivers of People with Alzheimer's Disease During the Transition to Institutionalization? Results from the New York University Caregiver Intervention Study.
Gaugler JE, Roth DL, Haley WE, Mittelman MS.
Center on Aging, Center for Gerontological Nursing, School of Nursing, University of Minnesota, Minneapolis, Minnesota, USA.

OBJECTIVES: To determine whether counseling and support reduce the burden and depressive symptoms of spouse caregivers of patients with Alzheimer's disease (AD) during the transition to institutionalization. DESIGN: A randomized, controlled trial of an enhanced counseling and support program for spouse caregivers of persons with AD. Structured interviews were conducted with spouse caregivers at baseline, every 4 months during Year 1, and every 6 months thereafter for up to 16 years. SETTING: Outpatient research clinic in the New York City metropolitan area. PARTICIPANTS: Referred volunteer sample of 406 spouse caregivers of community-dwelling patients with AD enrolled over a 9.5-year period. INTERVENTION: Enhanced counseling and support consisting of six sessions of individual and family counseling, support group participation, and continuous availability of ad hoc telephone counseling. MEASUREMENTS: Outcome measures included burden (modified Zarit Burden Interview) and depressive symptoms (Geriatric Depression Scale). RESULTS: Burden and depressive symptoms were significantly lower for caregivers in the treatment group than for controls receiving usual care at the time of and after institutionalization. Nursing home admission itself significantly reduced burden and depressive symptoms in the intervention and control groups. CONCLUSION: Institutionalization alone can reduce caregiver burden and depressive symptoms, but enhanced counseling provides additional long-term benefits. The results offer some of the first clinical evidence of the benefits of enhanced counseling during the transition to institutionalization for caregivers of people with AD.

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Psychol Med. 2008 Jan 4;:1-11 [Epub ahead of print]
Vagus nerve stimulation for depression: efficacy and safety in a European study.
Schlaepfer TE, Frick C, Zobel A, Maier W, Heuser I, Bajbouj M, O'Keane V, Corcoran C, Adolfsson R, Trimble M, Rau H, Hoff HJ, Padberg F, Müller-Siecheneder F, Audenaert K, Van den Abbeele D, Matthews K, Christmas D, Stanga Z, Hasdemir M.
Departments of Psychiatry and Mental Health, The Johns Hopkins University, Baltimore, MD, USA.

BACKGROUND: Vagus nerve stimulation (VNS) therapy is associated with a decrease in seizure frequency in partial-onset seizure patients. Initial trials suggest that it may be an effective treatment, with few side-effects, for intractable depression. METHOD: An open, uncontrolled European multi-centre study (D03) of VNS therapy was conducted, in addition to stable pharmacotherapy, in 74 patients with treatment-resistant depression (TRD). Treatment remained unchanged for the first 3 months; in the subsequent 9 months, medications and VNS dosing parameters were altered as indicated clinically. RESULTS: The baseline 28-item Hamilton Depression Rating Scale (HAMD-28) score averaged 34. After 3 months of VNS, response rates (50% reduction in baseline scores) reached 37% and remission rates (HAMD-28 score <10) 17%. Response rates increased to 53% after 1 year of VNS, and remission rates reached 33%. Response was defined as sustained if no relapse occurred during the first year of VNS after response onset; 44% of patients met these criteria. Median time to response was 9 months. Most frequent side-effects were voice alteration (63% at 3 months of stimulation) and coughing (23%). CONCLUSIONS: VNS therapy was effective in reducing severity of depression; efficacy increased over time. Efficacy ratings were in the same range as those previously reported from a USA study using a similar protocol; at 12 months, reduction of symptom severity was significantly higher in the European sample. This might be explained by a small but significant difference in the baseline HAMD-28 score and the lower number of treatments in the current episode in the European study.

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Am J Geriatr Psychiatry. 2008 Jan;16(1):58-64.
Treatment Outcomes for Older Depressed Patients With Earlier Versus Late Onset of First Depressive Episode: A Sequenced Treatment Alternatives to Relieve Depression (STAR*D) Report.
Kozel FA, Trivedi MH, Wisniewski SR, Miyahara S, Husain MM, Fava M, Lebowitz B, Zisook S, Rush AJ.
Department of Psychiatry, University of Texas Southwestern Medical Center (FAK, MHT, MMH, AJR), Dallas, TX; the Epidemiology Data Center, Graduate School of Public Health, University of Pittsburgh (SRW, SM), Pittsburgh, PA; the Department of Psychiatry, Harvard University, Massachusetts General Hospital (MF), Boston, MA; the Department of Psychiatry, University of California at San Diego (BL), San Diego, CA; the Department of Psychiatry, University of California at San Diego and San Diego VA Medical Center (SZ), La Jolla, CA; and the Department of Clinical Sciences, University of Texas Southwestern Medical Center (AJR), Dallas, TX.

Objective: Controversy exists whether age at onset of the first depressive episode predicts chance of response and remission or the timing of such outcome. In this study of older depressed outpatients, the authors evaluated whether the age at onset of the first major depressive episode (MDE) was related to clinical outcomes. Design: Post-hoc dataset analysis for older participants treated with citalopram in the Sequenced Treatment Alternatives to Relieve Depression trial was performed. Side effects, remission rates, and baseline characteristics were compared for participants whose first MDE began at or before age 55 (earlier onset) versus those with their first MDE after age 55 (late onset). Setting: Participants were enrolled from 23 psychiatric and 18 primary care settings. Participants: There were 574 treatment-seeking outpatients (age range: 55-75 years) with nonpsychotic major depressive disorder who had a baseline 17-item Hamilton Rating Scale for Depression score of >/=14. Intervention: Participants received citalopram treatment for up to 14 weeks. Measurements: Remission was defined by a 16-item Quick Inventory of Depressive Symptomatology-Self-Rated score of </=5 at study exit. Side effects were measured by the Frequency, Intensity, and Burden of Side Effects Rating. Results: Of 574 participants, 72.1% had earlier-onset depression and 27.9% had late-onset depression. Remission rates were not statistically different between earlier-onset (30.8%) and late-onset (31.9%) participants. Time to remission did not differ as well. Conclusion: The self-reported age at onset of the first MDE being after age 55 was not related to clinical outcomes for participants 55 to 75 years of age.

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Exp Clin Psychopharmacol. 2007 Dec;15(6):529-38.
Testosterone supplementation for depressed men: Current research and suggested treatment guidelines.
Kanayama G, Amiaz R, Seidman S, Pope HG.
Biological Psychiatry Laboratory, McLean Hospital.

Several lines of accumulating evidence suggest that testosterone might be effective for the treatment of depression, especially in older men who exhibit low testosterone levels. However, despite the potential promise of this approach, the available literature of controlled studies of testosterone in depression remains extremely limited. Therefore, testosterone treatment of depression must still be considered an experimental procedure. At the present state of research, it appears that testosterone might most likely show benefit as an augmentation strategy in men who exhibit low or borderline testosterone levels and who show only a partial response to conventional antidepressants. In this article, we provide some suggested practical guidelines for the treatment of such individuals. However, it should be recognized that these suggestions are tentative and will likely require revision as additional data become available. (PsycINFO Database Record (c) 2008 APA, all rights reserved).

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J Manag Care Pharm. 2007 Nov;13(9 Suppl A):S3-11.
Quest for timely detection and treatment of women with depression.
Alexander JL.
Psychiatry Women's Health Program, Kaiser Permanente, Northern California, Oakland, USA. Jeanne@afwh.org

BACKGROUND: Women are at risk for a wide range of depressive and anxiety disorders and particularly for mood disorders associated with their menstrual cycle, with seasonality, and during the menopausal transition. OBJECTIVE: To review the presentation of depression, the importance of timely and effective treatment, and some of the research surrounding increased prevalence of depression in women, and the times and conditions--such as the perimenopausal transition, pregnancy, postpartum period, and comorbidities--of this increased risk in women. SUMMARY: Dynamic interactions of both biological and environmental factors contribute to the development of major depression. These include, but are not limited to, predisposing genetic influences, gender, environmental stressors, poor social support, childhood sexual abuse, other psychiatric illness, and trauma. Timely and effective treatment of each episode of depression to remission is critically important. Barriers to instituting collaborative care of depressive illness are numerous. The lack of adequate collaborative care along with the consequent failure to adequately diagnose and treat depression reflects some of the deficiencies in the current organization and delivery of health services. CONCLUSION: The prevalence of depression, its psychosocial and medical consequences, and the worsening course of depression without treatment highlight the public health importance of early detection and improved strategies for the treatment of depression in modern health care settings.

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Nervenarzt. 2007 Nov;78 Suppl 3:551-63; quiz 564.
[Pharmacological therapy for therapy-resistant depression. New developments]
[Article in German]
Tadic A, Lieb K.
Klinik für Psychiatrie und Psychotherapie, Johannes-Gutenberg-Universität, Untere Zahlbacher Strasse 8, 55131 , Mainz. tadic@psychiatrie.klinik.uni-mainz.de

Remission, i.e. the complete absence of symptoms, is the major goal in the treatment of major depressive disorders because residual symptoms cause less functioning and a worse outcome. Despite several treatment steps, numerous patients do not reach complete remission of symptoms. In these patients, it is necessary to rule out several possible causes, including inadequate pharmacotherapy, to confirm the diagnosis of treatment-resistant depression (TRD). In the treatment of TRD, pharmacotherapy plays a central role. Nonpharmacological treatment strategies such as psychotherapy, electroconvulsive therapy, and other brain stimulation methods are also used for TRD treatment and are discussed elsewhere in this issue. Regarding complex pharmacotherapy of TRD, only a limited number of randomized-controlled trials have been done. In consequence, treatment decisions are often based on clinical experience, case series, and uncontrolled studies. Nevertheless, there are some interesting n
ew developments, which are summarized and assessed on the basis of existing evidence in this article. Afore, we present an overview of the most important definitions, epidemiologic data, diagnostic needs and methods for treatment optimization. We end with a critical view on the present and future development of antidepressant drugs.

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J ECT. 2007 Sep;23(3):169-74.
A questionnaire study of patients' experience of electroconvulsive therapy.
Myers DH.
From the Shelton Hospital, Shrewsbury, UK.

OBJECTIVE:: To ascertain patients' experience of electroconvulsive therapy (ECT) using a questionnaire having these features: short so to be acceptable to the elderly and the depressed; ascertaining experience, not opinions; coming from a 'neutral' source; and analyzed by methods that do not impose an arbitrary scale on ordinal response categories. METHOD:: Two hundred eighty-eight traceable patients consecutively treated with ECT were surveyed, the majority by post. One hundred forty-eight replied. RESULTS:: The conviction, a median of 4 years after ECT, that side effects persisted was related to current depression and, inversely, to age, but not to the number of ECT given. Current depression was also associated with a less favorable account of emotional support during ECT. Formal legal status had no effect on any of the answers, but refusal of, or agreement to ECT on sufferance, was linked to a relatively unfavorable view of it. Not all patients regarded the decision to give them ECT compulsorily wrong on principle; some judged by results. CONCLUSIONS:: The degree of current depression contributes to several aspects of the patient's view of ECT given a median of 4 years earlier. The belief that side effects persist has a complex basis; but the importance of this belief is not thereby diminished. Legal compulsion of treatment adds its own quota of contention which can be mitigated, but not entirely dispelled, by careful adherence to the law.

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J ECT. 2007 Sep;23(3):153-157.
Changes in Everyday and Semantic Memory Function After Electroconvulsive Therapy for Unipolar Depression.
Schat A, van den Broek WW, Mulder PG, Birkenhäger TK, van Tuijl R, Murre JM.
From the *Department of Psychology, University of Amsterdam, Amsterdam and Departments of †Psychiatry and ‡Epidemiology and Biostatistics, Erasmus Medical Centre, Rotterdam, The Netherlands.

OBJECTIVES:: This long-term prospective study focuses on the effects of electroconvulsive therapy (ECT) on everyday memory function and on semantic memory function. METHODS:: Results of memory test from 96 consecutive inpatients treated for unipolar depression were analyzed prospectively before ECT, after ECT treatment, and at 3- and 12-month follow-up. Everyday memory function was assessed by means of the Rivermead Behavioural Memory Test (RBMT) and semantic memory by 2 forms of the word fluency test. RESULTS:: In our study, age had a constant and significant negative effect on everyday memory (RBMT score) over time. Bilateral electrode placement mainly influenced everyday memory, which was significantly improved at 3-month follow-up. One year after discharge, the RBMT scores were not significantly different from pretreatment levels, indicating that ECT does not affect everyday memory on the longer term.Scores on both word fluency tests for semantic memory were significantly influenced by age over time. The effect of age changed from a negative influence directly after ECT to a positive effect at follow-up. This advantage of higher age indicates that the semantic memory of older patients receiving ECT for severe mood disorder shows greater improvement at follow-up compared with younger patients. Over time, the scores on only 1 of the word fluency tests were significantly influenced by mainly bilateral electrode placement. CONCLUSIONS:: A small but reversible decrease in everyday memory occurs after ECT in depressed patients, which is influenced by age and electrode placement. Semantic memory shows a fluctuating but recovering course, which is also influenced by age and electrode placement. During follow-up, the improvement in semantic memory was greater in the older patients.

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Am J Med. 2007 Sep;120(9):799-806.
Impact of cardiac rehabilitation on depression and its associated mortality.
Milani RV, Lavie CJ.
Department of Cardiology, Ochsner Medical Center, New Orleans, La 70121, USA. rmilani@ochsner.org

PURPOSE: Depression following major cardiac events is associated with higher mortality, but little is known about whether this can be reduced through treatment including cardiac rehabilitation and exercise training. We evaluated the impact of cardiac rehabilitation on depression and its associated mortality in coronary patients. PATIENTS AND METHODS: We evaluated 522 consecutive coronary patients (381 men, 141 women; aged 64+/-10 years) enrolled in cardiac rehabilitation from January 2000 to July 2005 and a control group of 179 patients not completing rehabilitation. Depressive symptoms were assessed by questionnaire at baseline and following rehabilitation, and mortality was evaluated after a mean follow-up of 1296+/-551 days. RESULTS: Prevalence of depressive symptoms decreased 63% following rehabilitation, from 17% to 6% (P <.0001). Depressed patients following rehabilitation had an over 4-fold higher mortality than nondepressed patients (22% vs 5%, P=.0004). Depressed patients who completed rehabilitation had a 73% lower mortality (8% vs 30%; P=.0005) compared with control depressed subjects who did not complete rehabilitation. Reductions in depressive symptoms and its associated mortality were related to improvements in fitness; however, similar reductions were noted in those with either modest or marked increases in exercise capacity. CONCLUSION: In patients following major coronary events, cardiac rehabilitation is associated with both reductions in depressive symptoms and the excess mortality associated with it. Moreover, only mild improvements in levels of fitness appear to be needed to produce these benefits on depressive symptoms and its associated mortality.

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J Am Geriatr Soc. 2007 Sep;55(9):1325-1332.
Maintenance Treatment for Old-Age Depression Preserves Health-Related Quality of Life: A Randomized, Controlled Trial of Paroxetine and Interpersonal Psychotherapy.
Dombrovski AY, Lenze EJ, Dew MA, Mulsant BH, Pollock BG, Houck PR, Reynolds CF 3rd.
Western Psychiatric Institute and Clinic, Department of Psychiatry, School of Medicine, University of Pittsburgh, and Advanced Center for Interventions and Services Research in Late-Life Mood Disorders, and John A. Hartford Center for Excellence in Geriatric Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

OBJECTIVES: To determine whether maintenance antidepressant pharmacotherapy and interpersonal psychotherapy sustain gains in health-related quality of life (HR-QOL) achieved during short-term treatment in older patients with depression. DESIGN: After open combined treatment with paroxetine and interpersonal psychotherapy, responders were randomly assigned to a two (paroxetine vs placebo) by two (monthly interpersonal psychotherapy vs clinical management) double-blind, placebo-controlled maintenance trial. HR-QOL outcomes were assessed over 1 year. SETTING: University-based clinic. PATIENTS: Of the referred sample of 363 persons aged 70 and older with major depression, 210 gave consent, and 195 started acute treatment; 116 met criteria for recovery, entered maintenance treatment, and were included in this analysis. INTERVENTIONS: Paroxetine; monthly manual-based interpersonal psychotherapy. MEASUREMENTS: Overall HR-QOL as measured using the Quality of Well-Being Scale (QWB) and six specific HR-QOL domains derived from the Medical Outcomes Study 36-item Short-Form Health Survey (SF-36) subscales. RESULTS: All domains of HR-QOL except physical functioning improved with successful acute and continuation treatment. After controlling for any effects of psychotherapy, pharmacotherapy was superior to placebo in preserving overall well-being (P=.04, effect size (r)=0.23), social functioning (P=.02, r=0.27), and role limitations due to emotional problems (P=.007, r=0.30). Interpersonal psychotherapy (controlling for the effects of pharmacotherapy) did not preserve HR-QOL better than supportive clinical management. CONCLUSION: Maintenance antidepressant pharmacotherapy is superior to placebo in preserving improvements in overall well-being achieved with treatment response in late-life depression. No such benefit was seen with interpersonal psychotherapy.

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Am J Psychiatry. 2007 Sep;164(9):1348-55.
Adjunctive Antidepressant Use and Symptomatic Recovery Among Bipolar Depressed Patients With Concomitant Manic Symptoms: Findings From the STEP-BD.
Goldberg JF, Perlis RH, Ghaemi SN, Calabrese JR, Bowden CL, Wisniewski S, Miklowitz DJ, Sachs GS, Thase ME.
128 East Avenue, Norwalk, CT 06851. JFGoldberg@yahoo.com.

OBJECTIVE: Practice guidelines have advised against treating patients with antidepressants during bipolar mixed states or dysphoric manias. However, few studies have examined the outcomes of patients with co-occurring manic and depressive symptoms who are treated with antidepressants plus mood stabilizing drugs. METHOD: The authors compared outcomes in patients with bipolar disorder who received a mood stabilizing agent with versus without an antidepressant for a bipolar depressive episode accompanied by >/=2 concurrent manic symptoms. The 335 participants were drawn from the first 2,000 enrollees in the National Institute of Mental Health (NIMH) Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). Kaplan-Meier survival curves and Cox regression models were used to compare time to recovery. General linear models examined the relationship between antidepressant use or mania symptom load at the study entry and mania or depression symptom severity at the 3-month follow-up. RESULTS: Adjunctive antidepressant use was associated with significantly higher mania symptom severity at the 3-month follow-up. The probability of recovery at 3 months was lower among patients with higher baseline depression severity. Antidepressant use neither hastened nor prolonged time to recovery once potential confounding factors were covaried in a Cox regression model. CONCLUSIONS: In bipolar depression accompanied by manic symptoms, antidepressants do not hasten time to recovery relative to treatment with mood stabilizers alone, and treatment with antidepressants may lead to greater manic symptom severity. These findings are consistent with those from the STEP-BD randomized trial for pure bipolar depression, in which adjunctive antidepressants did not yield higher recovery rates than did mood stabilizer monotherapy.

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Ann Clin Psychiatry. 2007 Jul-Sep;19(3):187-95.
The efficacy and tolerability of duloxetine in the treatment of anxious versus non-anxious depression: a post-hoc analysis of an open-label outpatient study.
Fava M, Martinez JM, Greist J, Marangell LB, Brown E, Chen L, Wohlreich MM.
Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.

Background. This study compares the efficacy and tolerability of 12 weeks of open-label duloxetine in adult outpatients with anxious versus non-anxious depression. Methods. Participants in a major depressive episode (N = 249) began duloxetine treatment at 30 or 60 mg daily for the first week, followed by up to 11 weeks of flexibly dosed duloxetine (60, 90, or 120 mg daily). Efficacy measures included HAMD(17), HAMA, and CGI-S. Safety and tolerability were assessed by early discontinuation and adverse event rates. Anxious depression was defined by a HAMD(17) Anxiety/Somatization Factor score >/= 7. Results. Duloxetine treatment was associated with a significantly greater reduction in total HAMD(17) scores and HAMD(17) Anxiety/Somatization Factor scores among patients with anxious depression compared to non-anxious depression. Differences in CGI-S and HAMA scores at the end of the trial between groups were not statistically significant. Remission and response rates at endpoint
were similar between groups, but anxious depressives had a significantly shorter median time to response. Discontinuation rates due to any reason, discontinuation due to adverse events, and treatment-emergent adverse events were similar between groups, except for the significantly greater occurrence of influenza in anxious depressives. Conclusions. Duloxetine's efficacy in anxious depression was somewhat superior to non-anxious depression; tolerability was comparable between groups.

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J Child Adolesc Psychopharmacol. 2007 Aug;17(4):407-20.
Efficacy and safety of atomoxetine in adolescents with attention-deficit/hyperactivity disorder and major depression.
Bangs ME, Emslie GJ, Spencer TJ, Ramsey JL, Carlson C, Bartky EJ, Busner J, Duesenberg DA, Harshawat P, Kaplan SL, Quintana H, Allen AJ, Sumner CR.
Lilly Research Laboratories, Indianapolis, Indiana.

This double-blind study examined efficacy and safety of atomoxetine (ATX; </=1.8mg/kg per day) in adolescents aged 12-18 with Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) diagnoses of both attention-deficit/hyperactivity disorder (ADHD) and co-morbid major depressive disorder (MDD). Diagnoses were confirmed by the Kiddie Schedule for Affective Disorders and Schizophrenia for School Age Children-Present and Lifetime Version and persistently elevated scores on the Attention-Deficit/Hyperactivity Disorder Rating Scale-IV, Parent version, Investigator-administered and -scored (ADHDRS-IV-Parent:Inv, >/=1.5 standard deviations above age and gender norms) and Children's Depression Rating Scale-Revised (CDRS-R, >/= 40). Patients were treated for approximately 9 weeks with ATX (n = 72) or placebo (n = 70). Mean decrease in ADHDRS-IV-Parent:Inv total score was significantly greater in the ATX group (-13.3 +/- 10.0) compared with the placebo group (-5.1 +/
- 9.9; p < 0.001). Mean CDRS-R score improvement was not significantly different between groups (ATX, -14.8 +/- 13.3; placebo, -12.8 +/- 10.4). Rates of treatment-emergent mania did not differ between groups (ATX, 0.0%; placebo, 1.5%). ATX treatment was associated with significantly more nausea and decreased appetite (p = 0.002; p = 0.003). No spontaneously reported adverse events involving suicidal ideation or suicidal behavior occurred in either group. ATX was an effective and safe treatment for ADHD in adolescents with ADHD and MDD. However, this trial showed no evidence for ATX of efficacy in treating MDD.

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Prog Neuropsychopharmacol Biol Psychiatry. 2007 Aug 3; [Epub ahead of print]
Open-label study of s-citalopram therapy of chronic fatigue syndrome and co-morbid major depressive disorder.
Amsterdam JD, Shults J, Rutherford N.
Depression Research Unit, Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA, United States.

OBJECTIVE: Chronic fatigue syndrome (CFS) is a debilitating disorder with prominent symptoms of malaise, fatigue, myalgia, arthralgia, and impaired concentration. The symptoms of CFS may often overlap those of Major Depressive Disorder (MDD). Treatment of CFS has generally been disappointing. We hypothesized that s-citalopram therapy may improve the symptoms of both disorders in CFS patients with co-morbid depression. METHODS: 16 patients received s-citalopram 10 mg to 20 mg daily for up to 12 weeks. Outcome measures of CFS included the Chalder Fatigue Questionnaire (CFQ), the multi-dimensional Fatigue Impact Scale (FIS), the CFS symptom rating (CFS-SR) 100 mm visual analogue scale, and the clinical global impressions severity (CGI/S) and change (CGI/C) ratings. Secondary outcomes of MDD included the Hamilton Depression Rating (HAM-D), Beck Depression Inventory (BDI), and the CGI/S and CGI/C ratings of MDD. RESULTS: We observed reductions in the mean CFQ score (p<0.0005), FIS score (p<0.0005), and CGI/S (p<0.0005) and CGI/C (p<0.0005) ratings over time. There was a significant improvement in 5 of the 8 CFS-SR symptoms: post-exertion malaise (p=0.001), headaches (p<0.0005), un-refreshing sleep (p<0.0005), and impaired memory and concentration (p<0.0005). There was also a reduction in mean HAM-D (p<0.0005), BDI (p<0.0005), CGI/S (p=0.001) and CGI/C (p<0.0005) ratings of MDD. LIMITATIONS: The sample size was limited and the study design was not double-blind or placebo controlled. CONCLUSION: We observed a significant reduction in both CFS and co-morbid MDD symptom severity ratings, and improvement in 5 of 8 core somatic symptoms of CFS during s-citalopram therapy.

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Behav Res Ther. 2007 Jul 24; [Epub ahead of print]
Sudden gains in interpersonal psychotherapy for depression.
Kelly MA, Cyranowski JM, Frank E.
Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, 3811 O’Hara Street, Pittsburgh, PA 15213, USA.

Sudden, precipitous improvements in depressive symptom severity have been identified as occurring among unipolar depressed individuals. These "sudden gains" have been associated with superior acute treatment outcome in several treatment modalities, including cognitive therapy. A better understanding of sudden gains may provide insight into the mechanisms of action in these and other psychotherapies. One efficacious therapy that has been overlooked in sudden gains research is interpersonal psychotherapy (IPT; Weissman, M. M., Markowitz, J. C., & Klerman, G. L. (2000). Comprehensive guide to interpersonal psychotherapy. New York: Basic Books). The present research examined the rates and concomitant features of sudden, precipitous improvements in depressive symptomotology among 185 women receiving IPT for recurrent depression. Sudden gains, defined using extant criteria for the Beck Depression Inventory, were assessed over 12 weeks of acute IPT treatment for depression and occurred for 33.5% of the sample. Sudden gains were not associated with diagnostic and demographic characteristics or with differential likelihood of achieving depression remission with IPT monotherapy during active treatment. Further, those with sudden gains were no more likely to maintain their recovery through maintenance treatment. The lack of impact of sudden gains on eventual outcome is discussed in terms of potentially disparate emphases and mechanisms of change between IPT and cognitive-behavioral therapy (CBT).

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Int J Neuropsychopharmacol. 2007 May 4;:1-13 [Epub ahead of print]
Efficacy of agomelatine, a MT1/MT2 receptor agonist with 5-HT2C antagonistic properties, in major depressive disorder.
Pierre Olie J, Kasper S.
Sainte Anne Hospital, University Department of Psychiatry, Paris, France.

Current antidepressants used in major depressive disorder (MDD) are still not efficacious enough for many patients due to high levels of treatment resistance and bothersome side-effects. Using a novel blinding method (interactive voice response system), this flexible-dosing study examined the effects of therapeutic doses of agomelatine, a new approach to depressive therapy offering potent melatonergic MT1/MT2 receptor agonism with 5-HT2C receptor antagonist properties, in patients with moderate-to-severe MDD. This 6-wk, double-blind, parallel-group study randomized 238 patients to 25 mg/d agomelatine (with dose adjustment at 2 wk to 50 mg/d in patients with insufficient improvement) or placebo. Depression severity was assessed using the Hamilton Depression Rating Scale (HAMD) and the Clinical Global Impression (CGI) scale. Agomelatine was significantly more efficacious than placebo, with an agomelatine-placebo difference of 3.44 (p<0.001) using the HAMD final total score. Compared with placebo, agomelatine also had a significant positive impact on CGI - Improvement (treatment difference=0.45) and CGI - Severity (treatment difference=0.50) (both p=0.006), response rate (54.3% vs. 35.5% with placebo, p<0.05) and time to first response (p=0.008). Similar results were seen in patients with the most severe MDD. Depressed mood and sleep items of the HAMD were also significantly improved with agomelatine, which was well tolerated with a safety profile similar to placebo at both doses. This study confirms that agomelatine is effective in treating major depression, including the most severely depressed patients, with a good safety and tolerability profile, therefore providing physicians with an effective pharmacological approach to antidepressant therapy.

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Med Health Care Philos. 2007 May 3; [Epub ahead of print]
Do antidepressants affect the self? A phenomenological approach.
Svenaeus F.
Center for Studies in Practical Knowledge, Department of Philosophy, Sodertorn University College, Huddinge, 141 89, Sweden, fredrik.svenaeus@sh.se.

In this paper, I explore the questions of how and to what extent new antidepressants (selective serotonin-reuptake inhibitors, or SSRIs) could possibly affect the self. I do this by way of a phenomenological approach, using the works of Martin Heidegger and Thomas Fuchs to analyze the roles of attunement and embodiment in normal and abnormal ways of being-in-the-world. The nature of depression and anxiety disorders - the diagnoses for which treatment with antidepressants is most commonly indicated - is also explored by way of this phenomenological approach, as are the basic structures of self-being. Special attention is paid in the analysis to the moods of boredom, anxiety and grief, since they play fundamental roles in depression and anxiety disorders and since their intensity and frequency appear to be modulated by antidepressants. My conclusion is that the effect of these drugs on the self can be thought of in terms of changes in self-feeling, or, more precisely, self-vibration of embodiment. I present the idea of a spectrum of bodily resonance, which extends from the normal resonance of the lived body, in which the body is able to pick up a wide range of different moods; continuing over various kinds of sensitivities, preferences and idiosyncrasies, in which certain moods are favored over others; to cases that we unreservedly label pathologies, in which the body is severely out of tune, or even devoid of tune and thus useless as a tool of resonance. Different cultures and societies favor slightly differently attuned self-styles as paradigmatic of the normal and good life, and the popularity of the SSRIs can therefore be explained, not only by defects of embodiment, but also by the presence of certain cultural norms in our contemporary society.

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Am J Psychiatry. 2007 May;164(5):768-77.
An intensive treatment program of interpersonal psychotherapy plus pharmacotherapy for depressed inpatients: acute and long-term results.
Schramm E, van Calker D, Dykierek P, Lieb K, Kech S, Zobel I, Leonhart R, Berger M.
University Medical Center Freiburg, Department of Psychiatry and Psychotherapy, Hauptstrasse 5, 79104 Freiburg, Germany. Elisabeth.Schramm@uniklinik-freiburg.de.

OBJECTIVE: The purpose of this article was to determine the relative efficacy of a psychotherapy program when combined with pharmacotherapy versus medication and clinical management in more severely depressed patients. METHOD: A randomized controlled trial was conducted in 124 hospitalized patients with DSM-IV major depressive disorder that compared 5 weeks of interpersonal psychotherapy modified for depressed inpatients (15 individual and eight group sessions) plus pharmacotherapy with a regimen that involved medication plus intensive clinical management. The study included a prospective, naturalistic follow-up 3 and 12 months after acute treatment in 97 of 105 treatment completers. The 17-item version of the Hamilton Depression Rating Scale (HAM-D) was the primary outcome measure. RESULTS: For the intent-to-treat cohort (N=124), analysis of covariance (ANCOVA) showed that patients treated with interpersonal psychotherapy had a significantly greater reduction of depressive symptoms at week 5. Response rates differed significantly between the two treatment conditions, favoring the group that received adjuvant interpersonal psychotherapy (70%) versus clinical management (51%). Remission rates also tended to be higher for patients in the interpersonal psychotherapy group (49% versus 34%). Patients who initially responded to interpersonal psychotherapy exhibited greater treatment gains at the 3-month follow-up evaluation, since only 3% of these subjects relapsed, compared with 25% of the clinical management subjects. Nine months later, this difference lost statistical significance. CONCLUSIONS: An inpatient treatment program with both brief and intensive psychotherapy plus pharmacotherapy is superior to standard treatment. The results, which add to a growing body of evidence, suggest that this combination treatment may offer an advantage over treatment with medication and clinical management for more severely depressed patients.

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Am J Psychiatry. 2007 May;164(5):761-767.
Randomized Trial of Weekly, Twice-Monthly, and Monthly Interpersonal Psychotherapy as Maintenance Treatment for Women With Recurrent Depression.
Frank E, Kupfer DJ, Buysse DJ, Swartz HA, Pilkonis PA, Houck PR, Rucci P, Novick DM, Grochocinski VJ, Stapf DM.
Western Psychiatric Institute and Clinic, 3811 O'Hara St., Pittsburgh, PA 15213. franke@upmc.edu.

OBJECTIVE: The authors sought to determine whether a greater frequency of interpersonal psychotherapy (IPT) sessions during maintenance treatment has a greater prophylactic effect than a previously validated once-a-month treatment. METHOD: A total of 233 women 20-60 years of age with recurrent unipolar depression were treated in an outpatient research clinic. After participants had achieved remission with weekly IPT or, if required, with weekly IPT plus antidepressant pharmacotherapy, they were randomly assigned to weekly, twice-monthly, or monthly maintenance IPT monotherapy for 2 years or until a recurrence of their depression occurred. RESULTS: Among participants who remitted with IPT alone and entered maintenance treatment (N=99), 19 (26%) of the 74 who remained in the study throughout the 2-year maintenance phase experienced a recurrence of depression. Among participants who required the addition of a selective serotonin reuptake inhibitor to achieve remission (N=90), 32 (36%) sustained that remission through continuation treatment and drug discontinuation and began maintenance treatment; of these, 13 (50%) of the 26 who remained in the study throughout the maintenance phase experienced a recurrence. Survival analysis of time to recurrence by randomized treatment frequency showed no effect on recurrence-free survival in either treatment subgroup. CONCLUSIONS: These results suggest that maintenance IPT, even at a frequency of only one visit per month, is a good method of prophylaxis for women who can achieve remission with IPT alone. In contrast, among those who require the addition of pharmacotherapy, IPT monotherapy represents a significantly less efficacious approach to maintenance treatment.

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Am J Psychiatry. 2007 May;164(5):753-60.
Acceptability of Second-Step Treatments to Depressed Outpatients: A STAR*D Report.
Wisniewski SR, Fava M, Trivedi MH, Thase ME, Warden D, Niederehe G, Friedman ES, Biggs MM, Sackeim HA, Shores-Wilson K, McGrath PJ, Lavori PW, Miyahara S, Rush AJ.
Epidemiology Data Center, Graduate School of Public Health, University of Pittsburgh, 127 Parran Hall, 130 DeSoto St., Pittsburgh, PA 15261. wisniew@edc.pitt.edu.

OBJECTIVE: Treatment of major depressive disorder typically entails implementing treatments in a stepwise fashion until a satisfactory outcome is achieved. This study sought to identify factors that affect patients' willingness to accept different second-step treatment approaches. METHOD: Participants in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial who had unsatisfactory outcomes after initial treatment with citalopram were eligible for a randomized second-step treatment trial. An equipoise-stratified design allowed participants to exclude or include specific treatment strategies. Analyses were conducted to identify factors associated with the acceptability of the following second-step treatments: cognitive therapy versus no cognitive therapy, any switch strategy versus any augmentation strategy (including cognitive therapy), and a medication switch strategy only versus a medication augmentation strategy only. RESULTS: Of the 1,439 participants who entered second-step treatment, 1% accepted all treatment strategies, 3% accepted only cognitive therapy, and 26% accepted cognitive therapy (thus, 71% did not accept cognitive therapy). Those with higher educational levels or a family history of a mood disorder were more likely to accept cognitive therapy. Participants in primary care settings and those who experienced a greater side effect burden or a lower reduction in symptom severity with citalopram were more likely to accept a switch strategy as compared with an augmentation strategy. Those with concurrent drug abuse and recurrent major depressive disorder were less likely to accept a switch strategy. CONCLUSIONS: Few participants accepted all treatments. Acceptance of cognitive therapy was primarily associated with sociodemographic characteristics, while acceptance of a treatment switch was associated with the results of the initial treatment.

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Am J Psychiatry. 2007 May;164(5):739-752.
Cognitive Therapy Versus Medication in Augmentation and Switch Strategies as Second-Step Treatments: A STAR*D Report.
Thase ME, Friedman ES, Biggs MM, Wisniewski SR, Trivedi MH, Luther JF, Fava M, Nierenberg AA, McGrath PJ, Warden D, Niederehe G, Hollon SD, Rush AJ.
University of Pittsburgh Medical Center, 3811 O'Hara St., Pittsburgh, PA 15213-2593. thaseme@upmc.edu.

OBJECTIVE: The authors compared the effectiveness of cognitive therapy and pharmacotherapy as second-step strategies for outpatients with major depressive disorder who had received inadequate benefit from an initial trial of citalopram. Cognitive therapy was compared with medication augmentation and switch strategies. METHOD: An equipoise-stratified randomization strategy was used to assign participants to either augmentation of citalopram with cognitive therapy (N=65) or medication (N=117; either sustained-release bupropion [N=56] or buspirone [N=61]) or switch to cognitive therapy (N=36) or another antidepressant (N=86; sertraline [N=27], sustained-release bupropion [N=28], or extended-release venlafaxine [N=31]). Treatment outcomes and the frequency of adverse events were compared. RESULTS: Less than one-third of participants consented to randomization strata that permitted comparison of cognitive therapy and pharmacotherapy. Among participants who were assigned to second-step treatment, those who received cognitive therapy (either alone or in combination with citalopram) had similar response and remission rates to those assigned to medication strategies. For those who continued on citalopram, medication augmentation resulted in significantly more rapid remission than augmentation with cognitive therapy. Among those who discontinued citalopram, there were no significant differences in outcome, although those who switched to a different antidepressant reported significantly more side effects than those who received cognitive therapy alone. CONCLUSIONS: After an unsatisfactory response to citalopram, patients who consented to random assignment to either cognitive therapy or alternative pharmacologic strategies had generally comparable outcomes. Pharmacologic augmentation was more rapidly effective than cognitive therapy augmentation of citalopram, whereas switching to cognitive therapy was better tolerated than switching to a different antidepressant.

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J Clin Psychiatry. 2007 Apr;68(4):582-7.
Addition of atomoxetine for depression incompletely responsive to sertraline: a randomized, double-blind, placebo-controlled study.
Michelson D, Adler LA, Amsterdam JD, Dunner DL, Nierenberg AA, Reimherr FW, Schatzberg AF, Kelsey DK, Williams DW.
Lilly Research Laboratories, Eli Lilly and Co., Indianapolis, Ind., USA. david_michelson@merck.com

OBJECTIVE: Despite appropriate treatment with selective serotonin reuptake inhibitors (SSRIs), many depressed patients do not attain remission. Addition of a noradrenergic intervention in patients poorly or partially responsive to SSRIs may improve outcomes, but few well-controlled studies testing this hypothesis have been reported. METHOD: Patients with major depressive disorder (confirmed by the Structured Clinical Interview for DSM-IV) were treated with sertraline at doses up to 200 mg/day in this study, conducted from June 18, 2003, to January 28, 2005. Patients who continued to experience depressive signs and symptoms after 8 weeks were randomly assigned to have atomoxetine 40 to 120 mg/day or placebo added to sertraline for a further 8 weeks. RESULTS: Of 276 patients starting the study, 146 with persistent depressive symptoms after 8 weeks of sertraline treatment (mean [SD] final sertraline dose: 161.1 [43.4] mg/day) were randomly assigned to addition of atomoxetine or placebo. After 8 additional weeks, there was no difference between treatment groups in mean change in symptom severity or in the proportion of patients whose symptoms remitted (sertraline/ atomoxetine 29/72 [40.3%], sertraline/placebo 28/74 [37.8%], p = .865). Secondary analyses that separated the subgroups with improvements in symptoms that did not reach remission (partial responders) and those with little or no improvement (nonresponders) also showed no effect of atomoxetine. The number of patients discontinuing because of adverse events did not differ between groups. CONCLUSION: In depressed patients with persistent symptoms after an initial trial of sertraline, addition of atomoxetine did not improve response more than placebo.

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J Consult Clin Psychol. 2007 Apr;75(2):267-76.
Progressive resistance to a selective serotonin reuptake inhibitor but not to cognitive therapy in the treatment of major depression.
Leykin Y, Amsterdam JD, DeRubeis RJ, Gallop R, Shelton RC, Hollon SD.
Department of Psychology, University of Pennsylvania, Philadelphia, PA 19104-6196, USA. leykin@psych.upenn.edu

Recent research suggests that there may be a reduction in therapeutic response after multiple administrations of antidepressant drug (AD) therapy in patients with major depressive disorder. This study assessed the response to AD therapy and cognitive therapy (CT) of patients with a history of prior AD exposures. A sample of 240 patients with moderate-to-severe major depressive disorder entered a randomized controlled trial comparing pharmacotherapy with paroxetine to CT. Treatment was administered for 16 weeks. History of prior AD exposure was assessed with structured interviews, self-report, and medical records. Analyses were conducted using hierarchical linear models on the intent-to-treat sample. After controlling for various demographic and clinical factors, more prior AD exposures predicted poor response to paroxetine therapy but not to CT, as measured by the Hamilton Rating Scale for Depression (Hamilton, 1960; Williams, 1988). Whereas CT outcome was not significantly related to the number of prior AD exposures, a higher number of prior AD exposures was significantly associated with a lower response to paroxetine. If these findings are replicated in methodologically rigorous studies of paroxetine and other antidepressants, CT should be recommended, in preference to AD, for patients with multiple prior AD exposures. Copyright 2007 APA, all rights reserved.

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Community Ment Health J. 2007 Jan 19; [Epub ahead of print]
The Trauma Recovery Group: A Cognitive-Behavioral Program for Post-Traumatic Stress Disorder in Persons with Severe Mental Illness.
Mueser KT, Bolton E, Carty PC, Bradley MJ, Ahlgren KF, Distaso DR, Gilbride A, Liddell C.
Department of Psychiatry, Dartmouth Medical School, New Hampshire-Dartmouth Psychiatric Research Center, 105 Pleasant St., Concord, NH, 03301, USA, kim.t.mueser@dartmouth.edu.

To address the problem of post-traumatic stress disorder (PTSD) in severe mental illness, the Trauma Recovery Group, a mixed gender cognitive-behavioral program, was developed and piloted at a community mental health center. The 21-week program includes breathing retraining, education about PTSD, cognitive restructuring, coping with symptoms, and making a recovery plan. Eighty clients were assessed at baseline and 41 provided follow-up data. Retention in the group was good: 59%. Treatment completers improved significantly in PTSD symptoms and diagnosis, depression, and post-traumatic cognitions, but dropouts did not. The results support the feasibility of the program and suggest it produces clinical benefits.

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J Am Geriatr Soc. 2007 Jan;55(1):75-80.
Treatment and prevention of depression after surgery for hip fracture in older people: randomized, controlled trials.
Burns A, Banerjee S, Morris J, Woodward Y, Baldwin R, Proctor R, Tarrier N, Pendleton N, Sutherland D, Andrew G, Horan M.
Division of Psychiatry, University of Manchester, Manchester, UK.

(See editorial comments by Drs. Barbara Kamholz and Jurgen Unutzer on pp 000-000.) OBJECTIVES: To evaluate the effect of a psychiatric intervention in treating depression (treatment study) and the effect of a psychological treatment in preventing depression (prevention study) after hip fracture in older people. DESIGN: Two linked randomized, controlled trials. SETTING: Orthopedic units in Manchester, England. PARTICIPANTS: Two hundred ninety-three older people who had undergone surgery for a fractured hip: 121 in the treatment study and 172 in the prevention study. MEASUREMENTS: The Geriatric Depression Scale and Hospital Anxiety and Depression Scale for mood, functional tests for mobility and pain measures. RESULTS: There was a slight reduction in depressive symptoms in the active arm of the treatment study. In the prevention study, there was no significant difference in incident depression between the psychological intervention and treatment as usual. There were no differences in the functional and pain outcomes. CONCLUSION: The results from these two randomized, controlled trials show that, after hip fracture surgery, no statistically significant benefits can be achieved from a psychiatric intervention in people who are depressed or a psychological intervention to prevent the onset of depression.

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Fortschr Neurol Psychiatr. 2007 Jan 17; [Epub ahead of print]
[Deep Brain Stimulation in the Treatment of Psychiatric Disorders.]
[Article in German]
Kuhn J, Huff W, Lee SH, Lenartz D, Sturm V, Klosterkotter J.
Klinik fur Psychiatrie und Psychotherapie, Klinikum der Universitat zu Koln.

As a well and long-established approach in the treatment of selected movement disorders, deep brain stimulation (DBS) is also increasingly considered a potential treatment method in the case of mental disorders. Only recently, a number of highly promising case reports and case series have been published, in which impressive therapeutic outcomes under application of DBS in otherwise treatment-resistant psychiatric illnesses are reported. The current article aims to provide a detailed synopsis of the DBS approach and more specifically its application to mental disorders. By means of a systematic literature search, all relevant treatment studies published to date and focusing on obsessive compulsive disorder, Tourette syndrome, major depression, anxiety disorder and autism were incorporated and evaluated with respect to the scientific evidence presented.

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Neuropsychobiology. 2007 Jan 17;54(3):152-159 [Epub ahead of print]
Escitalopram in the Long-Term Treatment of Major Depressive Disorder in Elderly Patients.
Kasper S, Lemming OM, de Swart H.
Medical University of Vienna, Vienna, Austria.

Aim: The primary aim was to investigate the long-term safety and tolerability of escitalopram (10 or 20 mg/day) treatment of elderly patients suffering from major depressive disorder. The secondary aim was to examine response to treatment, as measured by change in the Montgomery-Asberg Depression Rating Scale (MADRS) total score from study entry to each visit, using observed cases. Method: This extension trial included 225 patients who had completed an 8-week, double blind, placebo-controlled lead-in study, which was performed in outpatients in primary care and in specialist clinics. The intent-to-treat population comprised 223 patients. Results: The overall withdrawal rate was 24%. The most common reason for withdrawal was adverse events (9%). The 5 most common adverse events were accidental injury, rhinitis, weight increase, arthralgia and coughing, with an incidence ranging from 8 to 13%. No new types of adverse events were reported in this extension study compared to the 8-week lead-in study. The mean weight increased from 69.7 kg at study entry to 70.3 kg at endpoint. The percentage of patients in remission (MADRS total score </=12) increased from 48% at study entry to 72% by week 52. Conclusion: Escitalopram demonstrated a favourable tolerability profile during 52 weeks of open-label treatment of elderly patients, with further improvement in depressive symptoms. Copyright (c) 2006 S. Karger AG, Basel.

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J Affect Disord. 2007 Jan 15; [Epub ahead of print]
Open-label aripiprazole in the treatment of acute bipolar depression: A prospective pilot trial.
McElroy SL, Suppes T, Frye MA, Altshuler LL, Stanford K, Martens B, Leverich GS, Post RM, Keck PE Jr.
Psychopharmacology Research Program, University of Cincinnati College of Medicine, Cincinnati, Ohio, United States.

BACKGROUND: Increasing evidence indicates that some second-generation antipsychotics are efficacious in bipolar depression, but there are few data on this illness for the novel agent aripiprazole. METHODS: Aripiprazole response was prospectively assessed for 8 weeks with the Montgomery-Asberg Depression Rating Scale (MADRS), the Clinical Global Impression Scale Modified for Bipolar Illness (CGI-BP), and the Young Mania Rating Scale (YMRS) in 31 bipolar patients with acute depression inadequately responsive to 1 mood stabilizer. Side effects and body weight were also evaluated. Outcome measures were analyzed with repeated measures ANOVAs. RESULTS: Patients showed a significant decrease in mean MADRS total and CGI-BP-Depression Severity scores, but only 14 (45%) completed the 8-week trial. Thirteen (42%) patients met criteria for response (>/=50% reduction in MADRS total score), 11 (35%) patients met criteria for remission (final MADRS total score </=12), and 9 (29%) patients discontinued aripiprazole for side effects, most commonly akathisia (N=4). As a group, patients showed statistically insignificant weight gain (0.8+/-2.5 kg) over the 8-week trial. CONCLUSION: Aripiprazole was associated with beneficial effects on mood in some patients with bipolar depression, but also had a high discontinuation rate, primarily due to side effects. Double-blind, placebo-controlled studies are necessary to determine aripiprazole's efficacy, tolerability, and safety in bipolar depression.

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Prog Neuropsychopharmacol Biol Psychiatry. 2006 Dec 15; [Epub ahead of print]
Aripiprazole augmentation in treatment-resistant bipolar depression: Early response and development of akathisia.
Kemp DE, Gilmer WS, Fleck J, Straus JL, Dago PL, Karaffa M.
University Hospitals Case Medical Center, Case Western Reserve University, United States.

There is growing evidence that atypical antipsychotics may be effective in the treatment of acute bipolar depression. Results from randomized, placebo-controlled trials support the use of quetiapine monotherapy and a combination of olanzapine-fluoxetine in the depressed phase of bipolar disorder, while only limited data exists regarding the use of aripiprazole in this population. To assess the potential effectiveness of aripiprazole in treating acute bipolar depression, a chart review was conducted on 12 patients with treatment-resistant bipolar disorder (I, II, and not otherwise specified [NOS]) who received aripiprazole augmentation for the relief of an acute major depressive episode. After 8 weeks of treatment, 4 of 12 (33%) patients demonstrated a response, defined as a 50% reduction in the Montgomery-Asberg Depression Rating Scale (MADRS) score. In addition, 5 of 12 (42%) patients newly developed akathisia. This report, though limited by its small sample size and naturalistic design, suggests that the usefulness of aripiprazole in the treatment of bipolar depression may be limited by akathisia.
  
Previous Depression Research: 2002-2006   
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